EP0037078B1 - Verfahren zur Wärmebehandlung einer wässrigen Lösung, die den menschlichen Blutkoagulationsfaktor XIII enthält - Google Patents
Verfahren zur Wärmebehandlung einer wässrigen Lösung, die den menschlichen Blutkoagulationsfaktor XIII enthält Download PDFInfo
- Publication number
- EP0037078B1 EP0037078B1 EP81102255A EP81102255A EP0037078B1 EP 0037078 B1 EP0037078 B1 EP 0037078B1 EP 81102255 A EP81102255 A EP 81102255A EP 81102255 A EP81102255 A EP 81102255A EP 0037078 B1 EP0037078 B1 EP 0037078B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- acid
- factor xiii
- aqueous solution
- heat treatment
- solution containing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/1025—Acyltransferases (2.3)
- C12N9/104—Aminoacyltransferases (2.3.2)
- C12N9/1044—Protein-glutamine gamma-glutamyltransferase (2.3.2.13), i.e. transglutaminase or factor XIII
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
- A61L2/0011—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using physical methods
- A61L2/0023—Heat
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
- A61L2/04—Heat
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Definitions
- This invention relates to a process of heat treatment to inactivate the hepatitis virus in an aqueous solution the human blood coagulation factor XIII.
- the blood coagulation factor XIII (hereinafter referred to briefly as factor XIII) participates in the formation of a stable fibrin polymer in the final stage of blood coagulation mechanism, and is also called fibrin stabilizing factor. Under normal conditions it exists in an inactive form in the blood. However, in the event of formation of thrombin upon coagulation of blood after hemorrhage, the factor XIII becomes activated by the acti on of thrombin and calcium ion and strives for the stabilization of fibrin. Therefore, in a blood suffering from diminution or deficiency of the factor XIII, although the coagulation time shows a normal threshold, the formed fibrin clot is fragile, giving rise to characteristic phenomena such as secondary hemorrhage.
- the clinical applications of the factor XIII preparations include not only treatment for disorders due to congenital or acquired deficiency or diminution in factor XIII but also promotion of wound healing after surgical operations in a broad range.
- the factor XIII which is the subject of this invention, is also one of the human serum protein preparations and is likewise subject to contamination with hepatitis virus.
- the infective activity of hepatitis virus in serum protein preparations in general, particularly in albumin preparations may be controlled by the heat treatment at 60°C for 10 hours without causing the denaturation of albumin. Since the albumin preparation subjected to such a heat treatment has been clinically used with safety, the method of inactivating the hepatitis virus by the heat treatment at 60°C for 10 hours is now being adapted to other human serum protein preparations. However, in order to apply such a heat treatment, the substance being treated must be stable to the treatment.
- US-A-3,904,751 relates to a process for isolating Factor XIII for a human placenta.
- the process comprises subjecting a human placenta as starting material to extraction with a sodium chloride aqueous solution, precipitation with diamino-ethoxy-acridine lactate (Rivanol®), a lower alcohol fractionation and purification by .
- e-amino-caproic acid is contained in a developer and glucose is contained in a dialyzing liquid. That is, these substances are not used as a stabilizer at heat-treatment for inactivating hepatitis virus as in case of the present invention.
- US-A-3,931,399 relates to a process for isolating Factor XIII from human placenta.
- Said process comprises extracting human placenta with sodium chloride solution, adding diamino-ethoxy-acridine lactate (Rivanol®); recovering the resultant precipitate and dissolving it in dilute alkali metal chloride solution containing a complexing agent; adding a quaternary ammonium base to the solution to precipitate inactive materials; precipitating the active principal from solution with Rivanol®; again dissolving the precipitate in dilute alkali metal chloride solution containing a complexing agent; reprecipitating the active principal by adding solid ammonium sulfate; forming a paste between the precipitate and a dilute solution of a complexing agent; dialyzing the paste; gel filtering the dialyzed product; precipitating the active principal from the active fractions which ammonium sulfate; dissolving the precipitate in a neutral tris-
- glucose is added as a stabilizer of Factor XIII merely in the form of a solution as oppposed to the present invention, where glucose is added as a stabilizer of Factor XIII during the heat-treatment for the inactivation of the hepatitis virus.
- EP-A-0011739 relates to a process for concentrating blood coagulation Factor XIII derived from human placenta, which comprises removing a fraction precipitated from a crude globulin fraction obtained from human placenta at a pH of 6 to 9 in a concentration of 4 to 9% (W/V) of alkylene oxide polymer or copolymer having a molecular weight of 2,000 to 20,000, and then collecting the fraction precipitated at the same pH in a concentration of 20 to 30% (W/V) of the above-mentioned polymer or copolymer, and subjecting the resulting concentrated Factor XIII to heat-treatment for inactivating the hepatitis virus in the presence of 10-20% neutral amino acid, monosaccharide or sugar alcohol.
- the present invention relates to a process for heat-treatment of Factor XIII-containing aqueous solution for inactivating hepatitis virus in the copresence of 10-30% W/V of a principal stabilizer selected from neutral amino acid, monosaccharide and sugar alcohol and 10-30% W/V of auxiliary stabilizer selected from alkali metal and alkaline earth metal salts or organic carboxylic acids having 3-10 carbon atoms.
- a principal stabilizer selected from neutral amino acid, monosaccharide and sugar alcohol
- auxiliary stabilizer selected from alkali metal and alkaline earth metal salts or organic carboxylic acids having 3-10 carbon atoms.
- EP-A-0018561 discloses a process for heat-treatment of an aqueous solution containing blood coagulation factor II, VIII, XIII and anti- thrombin III as well as plasminogen for the purpose of inactivating hepatitis virus in the presence of an amino acid, monosaccharide, oligosaccharide or sugar alcohol.
- the present invention relates to a process for heat-treatment of Factor XIII comprising subjecting the solution containing Factor XIII in the presence of an auxiliary stabilizer selected from alkali metal and alkaline earth metal salts of organic carboxylic acids having 3-10 carbon atoms in addition to the same stabilizer as used in the reference.
- the present inventors subsequently found that in the above method of heat stabilization, the heat stability of factor XIII could be further improved by the supplementary addition of a specific organic carboxylic acid salt.
- the present invention has been accomplished on the basis of said finding.
- An object of this invention is to provide a novel heat treatment process in which the inactivation treatment of hepatitis virus in an aqueous solution containing the human blood coagulation factor XIII is carried out under those conditions which increase the thermal stability of said factor.
- a process for heat treatment characterized in that the heat treatment at 50° to 80°C of an aqueous solution containing the human blood coagulation factor XIII is carried out for 3 to 15 hours in the presence of 10 to 30% (W/V) of a principal stabilizer selected from the group consisting of neutral amino acids, monosaccharides and sugar alcohols and 10 to 30% (W/V) of an auxiliary stabilizer selected from alkali metal and alkaline earth metal salts of organic carboxylic acids having 3 to 10 carbon atoms.
- a principal stabilizer selected from the group consisting of neutral amino acids, monosaccharides and sugar alcohols
- an auxiliary stabilizer selected from alkali metal and alkaline earth metal salts of organic carboxylic acids having 3 to 10 carbon atoms.
- the factor XIII being heat treated is subject to no particular limitation, so far as it is originated from man. It is contained in blood plasma, platelet and placenta in comparatively large quantities and methods for its recovery from respective materials have been known [Loewy, A.G., Journal of Biological Chemistry, 236, 2625 (1961); Januszko, B.T., Nature, 191, 1093 (1961); Bohn, V.H., Blut, 25, 235 (1972)]. Of these materials, because of their high prices, blood plasma and platelet are unsuitable for the large scale production of factor XIII. Conversely, the placenta contains a comparatively large quantity of factor XIII and is easily available. Therefore, the recovery from the placenta is attracting most attention at present.
- Preparation of the factor XIII from the placenta can be carried out by several methods such as a method for purifying the factor XIII by a combined procedure involving gel filtration and fractionations using ammonium sulfate, 2- ethoxy-6,9-diaminoacridine lactate (acrinol) and alcohol [Blut, 25, 235 (1972)]; a method utilizing principally the ammonium sulfate fractionation technique (Japanese Patent Application "Kokai” (Laid-open) No. 59,018/1978), and a fractionation method employing an alkylene oxide polymer (Japanese Patent Application "Kokai” (Laid-open) No. 64,522/1980, European Patent Application EP-A-11739.
- factor XIII degree of purification of factor XIII is not specifically restricted, it is desirable to use an aqueous solution of factor XIII having an activity of 5 to 500 units/ml, as assayed by the method described in Thrombosis, Diathesis Haemorrhagica, 23, 455 (1970).
- the factor XIII content of the aqueous solution to be heat- treated is preferably 0.1 to 10% (W/V) in terms of protein and the pH of the solution is generally 5 to 10, preferably 6.5 to 8.5 and adjusted most preferably with a suitable buffer solution of a low salt concentration.
- the neutral amino acids, monosaccharides and sugar alcohols for use as principal stabilizers are described in detail in Japanese Patent Application "Kokai” (Laid-open) No. 59,018/1978.
- Nonlimitative examples include neutral amino acids such as glycine and analine, monosaccharides such as glucose, xylose, and fructose, and sugar alcohols such as mannitol, galactitol, glucosaminitol, sorbitol, and galacto- aminitol. They may be used each alone or in combinations.
- the amount to be added of principal stabilizers is generally 10% to 30% (W/V) in practice. If present in an amount less than 10% (W/V), the principal stabilizers will exhibit only unsatisfactory stabilizing effect.
- the organic carboxylic acid having 3 to 10 carbon atoms is used in the form of a salt as the auxiliary stabilizer according to this invention is a hydrocarbon moiety combined with a carboxyl group.
- the hydrocarbon moiety may be saturated or unsaturated. Examples of such hydrocarbon moieties include alkyl groups, aryl groups (e.g. phenyl group) and aralkyl groups.
- the number of carboxyl group may be singular or plural, preferably one or two.
- the carboxylic acid may contain a hydroxyl group as substituent.
- the salt of said organic carboxylic acid to be used in the present process may be any so far as it is physiologically acceptable, alkali metal salts (e.g. sodium salt and potassium salt) and alkaline earth metal salts (e.g. calcium salt) are employed and sodium salt and potassium salt are most preferred.
- Suitable organic carboxylic acid salts include physiologically acceptable alkali metal and alkaline earth metal salts, preferably alkali metal salts (sodium salts and potassium salts) or organic carboxylic acids having 3 to 10 carbon atoms, preferably of propanoic acid, butanoic acid, pentanoic acid, caprylic acid, caproic acid, malonic acid, succinic acid, glutaric acid, adipic acid, citric acid and mandelic acid. These salts are used each alone or in combinations.
- the amount to be added of an organic carboxylic acid salt is 10% to 30% (W/V). If the amount is below 10% (W/V), the effectiveness as an auxiliary stabilizer will be unsatisfactory.
- the temperature of heat treatment is 50° to 80°C, preferably 60°C and the time of heating is 3 to 15 hours, preferably 10 hours.
- the aqueous solution containing the factor XIII shows an electric conductivity two to five times as high as that of untreated solution. Consequently, before purification, the heat- treated aqueous solution is dialyzed, diluted, or centrifuged to separate the factor XIII as a precipitate. Then the purification may be performed in known ways. If the recovered factor XIII has a sufficiently high purity, it is made into medicinal preparations by customary pharmaceutical procedures such as sterile filtration, dispensation and lyophilization.
- factor XIII In the case of crude factor XIII, it is purified by a combination of known purification procedures for factor XIII, such as chromatography with an anion exchanger, treatment with a molecular sieve, and fractionation by use of PEG, acrinol or the like.
- a preparation of human factor XIII which has been recovered from a HBsAg (hepatitis virus antigen)-positive blood plasma was heat treated at 60°C for 10 hours under the conditions as herein specified.
- a portion of the preparation corresponding to a factor XIII activity of 500 unit was inoculated into a chimpanzee to observe the onset of hepatitis. After one month, no sign of hepatitis was observed.
- the heat treatment process of this invention is capable of perfectly inactivating the infectivity of hepatitis virus which is liable to contaminate the factor XIII preparation, a precious blood preparation, thereby causing no loss in factor XIII activity.
- the heat treatment according to this invention therefore, has a remarkable advantage in the commercial production of factor XIII preparations involving a virus inactivation step.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Developmental Biology & Embryology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Cell Biology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Claims (6)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP4005080A JPS56135418A (en) | 1980-03-27 | 1980-03-27 | Heat treatment of aqueous solution containing 8 factor of coagulation of blood derived from human |
JP40050/80 | 1980-03-27 |
Publications (3)
Publication Number | Publication Date |
---|---|
EP0037078A2 EP0037078A2 (de) | 1981-10-07 |
EP0037078A3 EP0037078A3 (en) | 1982-01-13 |
EP0037078B1 true EP0037078B1 (de) | 1984-03-14 |
Family
ID=12570076
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP81102255A Expired EP0037078B1 (de) | 1980-03-27 | 1981-03-25 | Verfahren zur Wärmebehandlung einer wässrigen Lösung, die den menschlichen Blutkoagulationsfaktor XIII enthält |
Country Status (4)
Country | Link |
---|---|
US (1) | US4327086A (de) |
EP (1) | EP0037078B1 (de) |
JP (1) | JPS56135418A (de) |
DE (1) | DE3162578D1 (de) |
Families Citing this family (52)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3043857A1 (de) * | 1980-11-21 | 1982-07-08 | Behringwerke Ag, 3550 Marburg | Verfahren zur herstellung von blutgerinnungsfaktoren und danach hergestellte praeparation der faktoren ii und vii |
DE3045153A1 (de) * | 1980-11-29 | 1982-07-08 | Behringwerke Ag, 3550 Marburg | Verfahren zur herstellung von blutgerinnungsfaktoren und danach hergestellte praeparation der faktoren ix und x |
JPS57140724A (en) | 1981-02-25 | 1982-08-31 | Green Cross Corp:The | Heat-treatment of aqueous solution containing cold insoluble globulin |
US4495278A (en) * | 1981-04-27 | 1985-01-22 | Baxter Travenol Laboratories, Inc. | Process for making novel blood clotting enzyme compositions |
JPS5874617A (ja) * | 1981-10-28 | 1983-05-06 | Green Cross Corp:The | 人由来血液凝固第7因子含有水溶液の加熱処理方法 |
US4845074A (en) * | 1982-05-13 | 1989-07-04 | Cedars Sinai Medical Center | Heat treatment of Factor VIII |
US4456590B2 (en) * | 1981-11-02 | 1989-05-30 | Heat treatment of lyphilized blood clotting factor viii concentrate | |
US4556558A (en) * | 1982-05-13 | 1985-12-03 | Cedars-Sinai Medical Center | Treatment of factor VIII concentrate to minimize the affect of undesirable microorganisms |
DE3230849A1 (de) * | 1982-08-19 | 1984-02-23 | Behringwerke Ag, 3550 Marburg | Pasteurisiertes human-fibrinogen (hf) und verfahren zu dessen herstellung |
JPS5967228A (ja) * | 1982-10-07 | 1984-04-16 | Green Cross Corp:The | 寒冷不溶性グロブリンの凍結乾燥方法 |
JPS59104326A (ja) * | 1982-12-04 | 1984-06-16 | Toyo Jozo Co Ltd | マクロライド抗生物質の安定な経口用製剤および安定化法 |
US4585654A (en) * | 1983-04-29 | 1986-04-29 | Armour Pharmaceutical Co. | Process for pasteurizing fibronectin |
US4727027A (en) * | 1983-05-02 | 1988-02-23 | Diamond Scientific Co. | Photochemical decontamination treatment of whole blood or blood components |
US5176921A (en) * | 1983-05-02 | 1993-01-05 | Diamond Scientific Co. | Method of blood component decontamination by glucose addition |
AT382078B (de) * | 1983-05-31 | 1987-01-12 | Immuno Ag | Verfahren zur herstellung von praeparationen aus menschlichem blutplasma |
DE3330770A1 (de) * | 1983-08-26 | 1985-03-14 | Behringwerke Ag, 3550 Marburg | Verfahren zur pasteurisierung von humanplasma |
US5281579A (en) * | 1984-03-23 | 1994-01-25 | Baxter International Inc. | Purified virus-free hemoglobin solutions and method for making same |
DE3419581A1 (de) * | 1984-05-25 | 1985-11-28 | Behringwerke Ag, 3550 Marburg | Verfahren zur gewinnung einer faktor xiii-praeparation sowie ihre verwendung |
JPH0669961B2 (ja) * | 1984-09-25 | 1994-09-07 | 株式会社ミドリ十字 | 免疫グロブリンの加熱処理方法 |
JPH0825902B2 (ja) * | 1985-02-21 | 1996-03-13 | 株式会社ミドリ十字 | γ−グロブリンの加熱処理方法 |
WO1987005220A1 (en) * | 1986-03-10 | 1987-09-11 | Rubinstein Alan I | A method for treating gammaglobulin |
DE3622642A1 (de) * | 1986-07-05 | 1988-01-14 | Behringwerke Ag | Einkomponenten-gewebekleber sowie verfahren zu seiner herstellung |
IL86417A (en) * | 1987-05-22 | 1992-09-06 | Armour Pharma | Process for the inactivation of pathogens in biological or pharmaceutical material by mixing with aqueous solution containing a sugar(alcohol)and neutral salts as stabilizers |
EP0357724B1 (de) * | 1988-02-18 | 1992-12-02 | Baxter International Inc. | Stabilisierte heparinlösung |
CA1331133C (en) * | 1988-03-01 | 1994-08-02 | Michael Jon Pikal | Pharmaceutical growth hormone formulations |
DE3829524A1 (de) * | 1988-08-31 | 1990-03-01 | Behringwerke Ag | Verwendung von transglutaminasen als immunsuppressiva |
JPH0650999B2 (ja) * | 1988-09-12 | 1994-07-06 | 日本商事株式会社 | 血液凝固因子安定化法 |
FR2650508A1 (fr) * | 1989-08-01 | 1991-02-08 | Fondation Nale Transfusion San | Colle pasteurisee pour reunir des tissus humain ou animal |
DE3939346A1 (de) * | 1989-11-29 | 1991-06-06 | Behringwerke Ag | Arzneimitel zur subkutanen oder intramuskulaeren applikation enthaltend polypeptide |
JPH03240738A (ja) * | 1990-02-20 | 1991-10-28 | Hoechst Japan Ltd | 糖尿病性壊疽治療剤 |
JPH04507108A (ja) * | 1990-05-07 | 1992-12-10 | バクスター、インターナショナル、インコーポレイテッド | 安定化されたヘパリン溶液 |
JP3337488B2 (ja) * | 1992-03-06 | 2002-10-21 | アベンティス ファーマ株式会社 | 切迫流産治療剤 |
AT402788B (de) * | 1993-08-03 | 1997-08-25 | Immuno Ag | Virussichere blutgerinnungsfaktor xiii-präparation |
GB9418092D0 (en) * | 1994-09-08 | 1994-10-26 | Red Cross Found Cent Lab Blood | Organic compounds |
DE19508192A1 (de) * | 1995-03-09 | 1996-09-12 | Behringwerke Ag | Stabile Transglutaminasepräparate und Verfahren zu ihrer Herstellung |
JPH08333277A (ja) * | 1995-06-05 | 1996-12-17 | Hoechst Japan Ltd | ヒト血液凝固第xiii因子の安定化された水性液製剤 |
RU2244556C2 (ru) | 1999-02-22 | 2005-01-20 | Юниверсити Оф Коннектикут | Новые не содержащие альбумин составы фактора viii |
US7297716B2 (en) * | 2000-10-23 | 2007-11-20 | Shanbrom Technologies, Llc | Enhanced production of blood components, blood cells and plasma without freezing |
US6881731B1 (en) * | 2000-10-23 | 2005-04-19 | Shanbrom Technologies, Llc | Enhancers for microbiological disinfection |
US7411006B2 (en) * | 2000-10-23 | 2008-08-12 | Shanbrom Technologies, Llc | Enhanced production of blood clotting factors and fibrin fabric |
US8389687B2 (en) | 2000-10-23 | 2013-03-05 | Shanbrom Technologies, Llc | Polyvinylpyrrolidone cryoprecipitate extraction of clotting factors |
MXPA03007069A (es) * | 2001-02-07 | 2004-10-15 | Shanbrom Tech Llc | Acido carboxilico tal como acido citrico para desinfectar o mejorar la produccion de productos sanguineos tales como el plasma, crioprecipitado y/o plaqueta. |
JP4680398B2 (ja) * | 2001-02-09 | 2011-05-11 | 朝日印刷株式会社 | 包装用箱と物品収容枠 |
EP1532983A1 (de) | 2003-11-18 | 2005-05-25 | ZLB Bioplasma AG | Immunoglobulinpräparationen mit erhöhter Stabilität |
JP4868457B2 (ja) * | 2007-06-28 | 2012-02-01 | シグマ紙業株式会社 | 包装容器 |
EP2268267B1 (de) * | 2008-04-21 | 2017-06-14 | Novo Nordisk Health Care AG | Trockene transglutaminase-zusammensetzung |
JP5069661B2 (ja) * | 2008-10-22 | 2012-11-07 | ツェー・エス・エル・ベーリング・ゲー・エム・ベー・ハー | ヒト血液凝固第xiii因子の安定化された水性液製剤 |
JP5779780B2 (ja) | 2008-11-07 | 2015-09-16 | バクスター・インターナショナル・インコーポレイテッドBaxter International Incorp0Rated | 第viii因子製剤 |
CA2788863C (en) | 2010-02-04 | 2020-07-07 | Reinhard Franz Bolli | Immunoglobulin preparation |
EP2361636A1 (de) | 2010-02-26 | 2011-08-31 | CSL Behring AG | Immunglobulinpräparat und Aufbewahrungssystem für ein Immunglobulinpräparat |
CN102924562B (zh) * | 2012-11-19 | 2014-07-23 | 成都蓉生药业有限责任公司 | 一种人凝血因子ⅷ的干热处理稳定剂及其用途 |
CN105879038B (zh) * | 2016-05-27 | 2020-03-27 | 成都蓉生药业有限责任公司 | 一种制备人凝血酶原复合物的干热处理稳定剂及其用途 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3904751A (en) * | 1970-12-22 | 1975-09-09 | Behringwerke Ag | Process for isolating a fibrin stabilizing factor from human placenta |
US3931399A (en) * | 1970-12-22 | 1976-01-06 | Behringwerke Aktiengesellschaft | Process for isolating a fibrin-stabilizing factor |
JPS51118820A (en) * | 1975-04-08 | 1976-10-19 | Green Cross Corp:The | A process for preparing heat stable macroglobulin |
JPS5359018A (en) * | 1976-11-10 | 1978-05-27 | Green Cross Corp:The | Concentrated xiii-th blood coagulating factor derived from human placentaand its preparation |
JPS6029687B2 (ja) * | 1978-11-07 | 1985-07-12 | 株式会社ミドリ十字 | ヒト胎盤由来血液凝固第103因子の濃縮液の製造方法 |
DE2916711A1 (de) * | 1979-04-25 | 1980-11-06 | Behringwerke Ag | Blutgerinnungsfaktoren und verfahren zu ihrer herstellung |
-
1980
- 1980-03-27 JP JP4005080A patent/JPS56135418A/ja active Granted
-
1981
- 1981-03-20 US US06/245,971 patent/US4327086A/en not_active Expired - Fee Related
- 1981-03-25 DE DE8181102255T patent/DE3162578D1/de not_active Expired
- 1981-03-25 EP EP81102255A patent/EP0037078B1/de not_active Expired
Also Published As
Publication number | Publication date |
---|---|
EP0037078A2 (de) | 1981-10-07 |
EP0037078A3 (en) | 1982-01-13 |
DE3162578D1 (en) | 1984-04-19 |
JPS56135418A (en) | 1981-10-22 |
JPS6236493B2 (de) | 1987-08-07 |
US4327086A (en) | 1982-04-27 |
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